Liu Y, Hernandez A M, Shibata D, Cortopassi G A
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033.
Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8910-4. doi: 10.1073/pnas.91.19.8910.
The background frequency of t(14;18) (q32;q21) chromosomal translocations at the locus associated with B-cell leukemia/lymphoma-2 (BCL2) was determined from a survey of the peripheral blood lymphocytes (PBLs) of 53 living individuals and from tissues of 31 autopsies by using a nested PCR assay. The translocation was detected in 55% of PBLs and 35% of autopsied spleens with a frequency of between less than 1 to 853 translocations per million cells. Translocations copurified with B lymphocytes. The frequency of translocations significantly increased with age in PBLs and spleens, as does human risk for lymphoma. Average translocation frequency was more than 40 times greater in the spleen and 13 times greater in the peripheral blood in the oldest individuals (61 yr and older) compared with the youngest individuals (20 yr or younger). Particular t(14;18)-bearing clones persisted over a period of 5 months in two individuals. These findings demonstrate that clones harboring the oncogenic t(14;18) chromosomal translocation are commonly present in normal humans, that such clones are long-lived, and that they rise in frequency with age. A multihit model of lymphomagenesis involving t(14;18) translocation followed by antigen stimulation is proposed.
通过巢式聚合酶链反应（PCR）检测，对53名在世个体的外周血淋巴细胞（PBL）以及31例尸检组织进行调查，以确定与B细胞白血病/淋巴瘤-2（BCL2）相关位点处t(14;18)（q32;q21）染色体易位的背景频率。在55%的PBL和35%的尸检脾脏中检测到易位，频率在每百万细胞少于1至853次易位之间。易位与B淋巴细胞共纯化。PBL和脾脏中易位频率随年龄显著增加，这与人类患淋巴瘤的风险情况相同。与最年轻个体（20岁及以下）相比，最年长个体（61岁及以上）脾脏中的平均易位频率高出40倍以上，外周血中高出13倍以上。在两名个体中，携带特定t(14;18)的克隆持续存在了5个月。这些发现表明，携带致癌性t(14;18)染色体易位的克隆在正常人体内普遍存在，这些克隆寿命较长，且其频率随年龄增加。提出了一种涉及t(14;18)易位后再经抗原刺激的淋巴瘤发生多打击模型。
